Open AccessA distinct epigenetic profile distinguishes stenotic from non-inflamed fibroblasts in the ileal mucosa of Crohn’s disease patients
Author(s) -
Andrew Y. F. Li Yim,
Jessica R. de Bruyn,
Nicolette W. Duijvis,
Catriona Sharp,
Enrico Ferrero,
Wouter J. de Jonge,
Ma E. Wildenberg,
Marcel M.A.M. Mannens,
Christianne J. Buskens,
Geert R. D’Haens,
Peter Henneman,
Anje A. te Velde
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0209656
Subject(s) - crohn's disease , epigenetics , intestinal mucosa , pathology , medicine , inflammatory bowel disease , disease , gastroenterology , biology , biochemistry , gene
Background The chronic remitting and relapsing intestinal inflammation characteristic of Crohn’s disease frequently leads to fibrosis and subsequent stenosis of the inflamed region. Approximately a third of all Crohn’s disease patients require resection at some stage in their disease course. As the pathogenesis of Crohn’s disease associated fibrosis is largely unknown, a strong necessity exists to better understand the pathophysiology thereof. Methods In this study, we investigated changes of the DNA methylome and transcriptome of ileum-derived fibroblasts associated to the occurrence of Crohn’s disease associated fibrosis. Eighteen samples were included in a DNA methylation array and twenty-one samples were used for RNA sequencing. Results Most differentially methylated regions and differentially expressed genes were observed when comparing stenotic with non-inflamed samples. By contrast, few differences were observed when comparing Crohn’s disease with non-Crohn’s disease, or inflamed with non-inflamed tissue. Integrative methylation and gene expression analyses revealed dysregulation of genes associated to the PRKACA and E2F1 network, which is involved in cell cycle progression, angiogenesis, epithelial to mesenchymal transition, and bile metabolism. Conclusion Our research provides evidence that the methylome and the transcriptome are systematically dysregulated in stenosis-associated fibroblasts.